Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

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Drug-Drug Interactions

Drug Interactions between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

Last Updated: October 17, 2017; Last Reviewed: October 17, 2017

Table 18c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or if a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.

Note: Interactions associated with didanosine (ddI) and stavudine (d4T) are not included in this table. Please refer to Food and Drug Administration product labels for information regarding interactions between ddI or d4T with other concomitant drugs.

Table 18c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
Concomitant Drug Class/Name NRTI Effect on NRTI and/or Concomitant Drug Concentrations Dosage Recommendations and Clinical Comments
Cytomegalovirus and Hepatitis B Antivirals
Adefovir TDF No data Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may be increased.
Ganciclovir,
Valganciclovir
TDF No data Serum concentrations of these drugs and/or TDF may increase. Monitor for dose-related toxicities.
ZDV No significant effect Potential increase in hematologic toxicities.
Hepatitis C Antiviral Agents
Ledipasvir/sofosbuvir,
sofosbuvir/velpatasvir,
sofosbuvir/ velpatasvir/ voxilaprevir
TAF No significant effect No dose adjustment.
TDF Ledipasvir ↑ TDF AUC 40%–98% when TDF given with RPV and EFV

Further ↑ TDF possible if TDF given with PIs
No dose adjustment necessary.

General recommendations:
The safety of increased TDF exposure when ledipasvir/sofosbuvir is coadministered with TDF and a PI/r, ATV/c, or DRV/c has not been established. Consider alternative HCV or ARV drugs to avoid increased TDF toxicities.

Consider using TAF in patients at risk of TDF-associated adverse events. If coadministration with TDF is necessary, monitor for TDF toxicity.

Coadministration of ledipasvir/sofosbuvir with EVG/c/TDF/FTC is not recommended.
Glecaprevir/ Pibrentasvir TAF, TDF No significant effect No dose adjustment.
Ribavirin ZDV Ribavirin inhibits phosphorylation of ZDV. Avoid coadministration if possible, or closely monitor HIV virologic response and possible hematologic toxicities.
INSTIs
DTG TAF TAF AUC ↔ No dose adjustment.
TDF TDF AUC ↔

DTG AUC ↔
No dose adjustment.
RAL TDF RAL AUC ↑ 49% No dose adjustment.
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, TDF, TAF, ZDV No significant effect No dose adjustment.
Methadone ABC Methadone clearance ↑ 22% No dose adjustment.
ZDV ZDV AUC ↑ 29%–43% Monitor for ZDV-related adverse effects.
Other
Atovaquone
ZDV ZDV AUC ↑ 31% Monitor for ZDV-related adverse effects.
Anticonvulsants
Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
TAF With carbamazepine:
  • TAF AUC ↓ 55%

↓ TAF possible with other anticonvulsants
Consider alternative anticonvulsant.
Antimycobacterial
Rifabutin, rifampin, rifapentine
TAF ↓ TAF possibled Coadministration is not recommended.
Herbal Products
St. John's wort
TAF ↓ TAF possible Coadministration is not recommended.
PIs (HIV)
ATV (unboosted), ATV/c, ATV/r TAF TAF 10 mg with ATV/r:
  • TAF AUC ↑ 91%
TAF 10 mg with ATV/c:
  • TAF AUC ↑ 75%
No dose adjustment (use TAF 25 mg).
TDF With ATV (Unboosted):
  • ATV AUC ↓ 25% and Cmin ↓ 23% to 40% (higher Cmin with RTV than without RTV)

TDF AUC ↑ 24% to 37%
Avoid concomitant use without RTV or COBI.

Dose:
  • ATV 300 mg daily+ (RTV 100 mg or COBI 150 mg) daily when coadministered with TDF 300 mg daily. 
  • If using TDF and H2 receptor antagonist in ART-experienced patients, use ATV 400 mg daily + (RTV 100 mg or COBI 150 mg) daily.

Monitor for TDF-associated toxicity. 
ZDV With ATV (Unboosted):
  • ZDV Cmin ↓ 30% and AUC ↔
Clinical significance unknown.
DVR/c TAF TAF 25 mg with DRV/c:
  • TAF AUC ↔
No dose adjustment.
TDF ↑ TDF possible Monitor for TDF-associated toxicity.
DRV/r TAF TAF 10 mg with DRV/r:
  • TAF ↔
No dose adjustment.
TDF TDF AUC ↑ 22% and Cmin ↑ 37% Clinical significance unknown. Monitor for TDF toxicity.
LPV/r TAF TAF 10 mg with DRV/r:
  • TAF AUC ↑ 47%
No dose adjustment.
TDF LPV/r AUC ↓ 15%

TDF AUC ↑ 34%
Clinical significance unknown. Monitor for TDF toxicity.
TPV/r ABC ABC AUC ↓ 35%–44% Appropriate doses for this combination have not been established.
TAF ↓ TAF expected Coadministration is not recommended.
TDF TDF AUC ↔

TPV/r AUC ↓ 9%–18% and Cmin ↓ 12%–21%
No dose adjustment.
ZDV ZDV AUC ↓ 35%

TPV/r AUC ↓ 31%–43%
Appropriate doses for this combination have not been established.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATC/c = atazanavir/cobicistat; AUC = area under the curve; Cmin = minimum plasma concentration; COBI, c = cobicistat; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; FTC = emtricitabine; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitors; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV, r = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

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